Poly(ADP-ribose) protects vascular smooth muscle cells from oxidative
DNA damage |
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Authors: | Chao Zhang Tao Luo Shijun Cui Yongquan Gu Chunjing Bian Yibin Chen Xiaochun Yu Zhonggao Wang |
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Institution: | 1.Vascular Surgery Department of Xuanwu Hospital, Institute of Vascular Surgery, Capital Medical University, Beijing 100053, China.;2.Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA |
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Abstract: | Vascular smooth muscle cells (VSMCs) undergo death during atherosclerosis, a
widespread cardiovascular disease. Recent studies suggest that oxidative damage
occurs in VSMCs and induces atherosclerosis. Here, we analyzed oxidative damage
repair in VSMCs and found that VSMCs are hypersensitive to oxidative damage.
Further analysis showed that oxidative damage repair in VSMCs is suppressed by a
low level of poly (ADP-ribosyl)ation (PARylation), a key post-translational
modification in oxidative damage repair. The low level of PARylation is not
caused by the lack of PARP-1, the major poly(ADP-ribose) polymerase activated by
oxidative damage. Instead, the expression of poly(ADP-ribose) glycohydrolase,
PARG, the enzyme hydrolyzing poly(ADP-ribose), is significantly higher in VSMCs
than that in the control cells. Using PARG inhibitor to suppress PARG activity
facilitates oxidative damage-induced PARylation as well as DNA damage repair.
Thus, our study demonstrates a novel molecular mechanism for oxidative
damage-induced VSMCs death. This study also identifies the use of PARG
inhibitors as a potential treatment for atherosclerosis. BMB Reports 2015;
48(6): 354-359] |
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Keywords: | DNA damage Oxidative stress Poly(ADP-ribosyl)ation Poly(ADP-ribose) glycohydrolase Vascular smooth muscle cells |
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